The human intestine, thought to be initially sterile in utero, is exposed to a large variety of maternal and environmental microbes immediately after birth. The subsequent colonization and succession events in the gut remain dynamic during the first years of life, after which the microbiota becomes adult-like and relatively stable (1). The human gut microbiota contains more than 500 different phylotypes belonging essentially to two major bacterial divisions, the Bacteroidetes and the Firmicutes (2). The successful symbiotic relationships arising from bacterial colonization of the human gut have yielded a wide variety of metabolic, structural, protective and other beneficiary functions. The enhanced metabolic activities of the colonized gut ensure that dietary components, which are otherwise indigestible, are degraded with released byproducts providing an important nutrient source for the host. Similarly, the immunological importance of the gut microbiota is well-recognized and exemplified in germfree animals which have an impaired immune system that is functionally reconstituted following the introduction of commensal bacteria (3-5).
In sharp contrast to the production of secretory intestinal IgA which is influenced by microbial colonization per se (6, 7), T cell development and differentiation seems to require colonization of specific commensal micro-organisms. Clostridium species, in particular the spore-forming segmented filamentous bacteria (SFB), appear to be a major driver for the maturation of intestinal Th1, Th17 and Tregs (8, 9). Recent studies have, however, now shown that other gut bacteria including those of the altered Schaedler flora can induce de novo generation of Tregs while mono-colonization with Bacteroides fragilis can correct the Th1/Th2 imbalance in germfree mice by promoting the expansion of Tregs (5, 10).
The present invention seeks to elucidate other resident gut bacteria that can modulate metabolic activity in the gut and/or play a role in immunoregulatory processes.